1952. Second Time’s the Charm? Low Yield of 3 AFB Smears among Inpatients Evaluated for Pulmonary Tuberculosis

Abstract Background Among inpatients with suspected tuberculosis (TB), CDC and IDSA guidelines recommend collecting three respiratory specimens 8-24 hours apart for acid-fast bacilli (AFB) smear and mycobacterial culture. However, data supporting this approach are limited, particularly in the era of Xpert MTB/RIF PCR assays (Xpert). Our objective was to estimate the sensitivity of 1, 2, or 3 AFB smears +/- Xpert to detect pulmonary TB in a low incidence setting. Methods We conducted a retrospective study of inpatients at a large U.S. academic medical center with mycobacterial culture performed on one or more respiratory specimens July 2016 – December 2022. AFB smear microscopy, Xpert, or both, were performed on each specimen. We evaluated percent positivity on serial AFB smears and on Xpert among patients with confirmed TB, as well as the yield of a third AFB smear among all patients tested. Results A total of 7,445 inpatients underwent 15,710 mycobacterial cultures on respiratory specimens, of whom 52 (0.7%) were diagnosed with culture-positive pulmonary TB (Figure 1). Among patients with TB, the first AFB smear was positive in 22/52 (42%) cases and a second AFB smear was positive in 5/24 (21%) cases; there were no cases in which a third AFB smear was positive after two initial negative smears (Table 1). Among 1,523 instances in which a third specimen was obtained among patients with and without TB, the third sample yielded a diagnosis of TB by culture in 1 case. Overall sensitivity to detect a positive AFB smear or Xpert result among patients with TB was equivalent between 2 and 3 AFB smear pathways at 52%. Overall sensitivity to detect TB prior to culture positivity was highest with addition of an Xpert to 2 or 3 AFB smears at 67% (Table 2). Conclusion In a low incidence setting, TB screening with 2 AFB smears offers the same diagnostic yield as with 3 AFB smears while potentially reducing laboratory burden and duration of patient isolation. Xpert demonstrated high sensitivity for detection of TB, and it increased sensitivity to detect TB when added to AFB smear-based screening alone. However, a quarter of patients with TB diagnosed by mycobacterial culture were not detected by AFB smear or PCR, highlighting the importance of using clinical judgement when discontinuing isolation. Disclosures Emily P. Hyle, MD MSc, UpToDate.com: Royalties Molly L. Paras, MD, Angiodynamics: Honoraria|Angiodynamics: Honoraria

Background.Among inpatients with suspected tuberculosis (TB), CDC and IDSA guidelines recommend collecting three respiratory specimens 8-24 hours apart for acid-fast bacilli (AFB) smear and mycobacterial culture.However, data supporting this approach are limited, particularly in the era of Xpert MTB/RIF PCR assays (Xpert).Our objective was to estimate the sensitivity of 1, 2, or 3 AFB smears +/-Xpert to detect pulmonary TB in a low incidence setting.
Methods.We conducted a retrospective study of inpatients at a large U.S. academic medical center with mycobacterial culture performed on one or more respiratory specimens July 2016 -December 2022.AFB smear microscopy, Xpert, or both, were performed on each specimen.We evaluated percent positivity on serial AFB smears and on Xpert among patients with confirmed TB, as well as the yield of a third AFB smear among all patients tested.
Results.A total of 7,445 inpatients underwent 15,710 mycobacterial cultures on respiratory specimens, of whom 52 (0.7%) were diagnosed with culture-positive pulmonary TB (Figure 1).Among patients with TB, the first AFB smear was positive in 22/52 (42%) cases and a second AFB smear was positive in 5/24 (21%) cases; there were no cases in which a third AFB smear was positive after two initial negative smears (Table 1).Among 1,523 instances in which a third specimen was obtained among patients with and without TB, the third sample yielded a diagnosis of TB by culture in 1 case.Overall sensitivity to detect a positive AFB smear or Xpert result among patients with TB was equivalent between 2 and 3 AFB smear pathways at 52%.Overall sensitivity to detect TB prior to culture positivity was highest with addition of an Xpert to 2 or 3 AFB smears at 67% (Table 2).

Conclusion.
In a low incidence setting, TB screening with 2 AFB smears offers the same diagnostic yield as with 3 AFB smears while potentially reducing laboratory burden and duration of patient isolation.Xpert demonstrated high sensitivity for detection of TB, and it increased sensitivity to detect TB when added to AFB smearbased screening alone.However, a quarter of patients with TB diagnosed by mycobacterial culture were not detected by AFB smear or PCR, highlighting the importance of using clinical judgement when discontinuing isolation.
1 Johns Hopkins University School of Medicine, Baltimore, MD 2 Pumas AI, Inc, Centreville, Virginia 3 Johns Hopkins, Baltimore, Maryland 4 University of Florida College of Pharmacy, Gainesville, Florida 5 Rutgers New Jersey Medical School, Newark, New Jersey 6 University of Maryland School of Pharmacy, Baltimore, Maryland 18 F-pretomanid, 18 F-sutezolid, 18 F-linezolid and 76 Br-bedaquiline) active against MDR strains to measure multicompartmental exposures (area under the curve, AUC).Each radioanalog is chemically identical to the parent antibiotic and the radioisotope is retained within the major metabolite.PET facilitated pharmacokinetic modeling predicted tissue exposures which were used to design optimized regimens (Fig. 1).lung/plasma ∼1), only 18 F-pretomanid achieved high brain exposures (Fig. 2).First-in-human 18 F-pretomanid PET studies (n = 6 subjects) also demonstrated high exposures in both lung and brain compartments (Fig. 3).Pharmacokinetic modeling confirmed equivalence between mouse and human PET studies and identified the human pretomanid dose necessary to attain therapeutic brain exposures.Several pretomanid-based regimens demonstrated excellent bactericidal activity, equivalent or better than the standard TB regimen in the mouse model of TB meningitis, with addition of pyrazinamide significantly improving the activity of all regimens (Fig. 4).